This Gordon Conference is aimed at a serious national and international problem: the lack of new antimicrobial agents for treatment of multi-resistant bacterial infections. In both the Intensive Care Unit (ICU) and the community, organisms commonly causing serious infections have become resistant to many of our most effective antibiotics. In the community, organisms such as Streptococcus pneumonia have a rate of non- susceptibility to -lactam antibiotics exceeding 20%. Other effective agents, such as macrolides, have resistance rates on the order of 40%. Community-Acquired MRSA has exploded in prevalence across the United States and the globe and is commonly seen in emergency rooms. In the ICU, MRSA makes up approximately 50% of all Staphylococcus aureus infections and we have seen the advent of multi-resistant Gram-negative organisms, so that even common pathogens such as Klebsiella and E. coli may carry extended-spectrum -lactamases, rendering them resistant to many of our best agents and, in the case of KPC -lactamases, this resistance profile includes carbapenems. In the case of Pseudomonas aeruginosa and Acinetobacter species, it is now reasonably common for an infecting pathogen to be resistant to all licensed antibiotics. A measure of the clinical desperation is that we have resurrected 50-year old, relatively toxic agents (colistin/polymixins) to have at least one available therapeutic intervention. In this Gordon Research Conference, we have a unique cross-disciplinary approach to the problem, where chemists, basic biologists and translational scientists meet and where Industry, Academia, Regulatory Agencies and political observers are all stakeholders and are invited to contribute to the interchange. Our past meetings have been scientifically rigorous and open, with both new science coming forward and the identification of bottlenecks in the process being part of the process. We have a conference where we are dedicated to the broadest participation and, in specific, are desirous of inclusion of younger members of the field at the post-doctoral level, to bring fresh perspectives to the problems being examined. The site of the meeting is well-suited for this interchange and the structure of the conference follows the classical Gordon Conference format. The Discussion Leaders have been chosen with an eye toward generating robust, insightful discussion after the presentations. The format is democratic, so that all voices will be heard and the emphasis will be on presenting the best and newest science and asking the correct questions to push the field forward. In this grant application, we ask for partial financial support to defray the costs associated with this importan undertaking. PUBLIC HEALTH RELEVANCE: Antibiotic resistance is widespread globally, creating daily challenges clinically; yet prospects for discovery and development of future generations of antibiotics are bleak, as Big Pharma is exiting the field. There have been no new classes of Gram-negative antibiotics for many years and prospects for effective treatment of infections by Gram-positive bacteria are diminishing too. This crisis has national and international repercussions and it is the focus of this Gordon Research Conference to bring all the stakeholders together to identify the best way forward in the discovery and development of new antimicrobial agents.